Endogenous Liver Protections Against Lipotoxicity and Oxidative Stress to Avoid the Progression of Non-alcoholic Fatty Liver to more Serious Disease

Abstract

: Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by an ectopic accumulation of lipids in at least 5% of hepatocytes. The first phase of the disease, called hepatic steatosis, progresses over time to chronic conditions such as steatohepatitis, cirrhosis, and hepatic insufficiency and cancer. The accumulation of free fatty acids in hepatocytes, particularly saturated fatty acids, is a key process in the development and progression of NAFLD. Furthermore, the accumulation of oxidative stress markers in NAFLD is closely linked to lipotoxicity due to impaired lipid metabolism and increased generation of reactive oxygen species (ROS). However, endogenous mechanisms are activated early in the liver to protect against lipotoxicity and oxidative stress, thus preventing liver mass loss and disease progression. Thus, in order to develop appropriate therapies, the purpose of this review is to discuss recent data from the literature regarding the importance of intrinsic mechanisms deployed by the liver in protecting itself against the adverse effects related to chronic lipid accumulation and ROS generation.

Effects of blended oils with different n-6/n-3 polyunsaturated fatty acid ratios on high-fat diet-induced metabolic disorders and hepatic steatosis in rats

“…Hepatic steatosis is the initial stage of NAFLD, which is a metabolic disorder characterized by ectopic accumulation of lipids in liver cells (Barrios-Maya et al, 2022). N-3 PUFAs played an important role in regulating fat accumulation and fat elimination in the liver, and the disorder of n-6/n-3 PUFA ratio in the liver affected the histological pattern by regulating the amount of liver lipids (El-Badry et al, 2007).…”

Drosophila melanogaster as a Biotechnological Tool to Investigate the Close Connection Between Fatty Diseases and Pesticides

“…Studies indicated that lipotoxicity correlates with the production of toxic lipid metabolites, such as ceramides, lysophosphatidylcholine, diacylglycerol and metabolites of cholesterol [39,40]. At the same time, lipotoxicity triggers the oxidative stress process and the production of reactive oxygen species (ROS), which alters mitochondrial function [41,42]. Mitochondrial dysfunction decreases ATP production and further increases the accumulation of toxic lipid intermediates, which accentuate the production of ROS and cell death mechanisms [32,40].…”